Primary diterpene-alcohol



Patented Apr. 23, 1935 UNITED STATES PATENT OFFICE PBIBIARY DITERPENE-ALCOHOL Leopold Ruzicka, Zurich Switzerland, assignmto Society of Chemical Industry in Baslc, Basel,

Switzerland No Drawing.

3 Claims.

ApplicationMarch 2, 1934, Serial In Switzerland March 3, 1933 manner, yields the ketone V. The latter by con densation with acetylene in presence of alkali amide, as well as by the partial hydrogenization, conducted as described above, of the acetylene alcohol VI passes into the tertiary diterpene-alcohcl VII. This is transposed by heating it with an acid anhydride, for instance acetic anhydride, into the ester of the isometric diterpene-alcohol VIII.- By alkaline saponification of the ester and 1130 0113 E30 CH: H3O CH3 i H2O C CH3 CH2 H20 C "CH3 CH HnC C CH3 CH2 I I ll/ CH3 1 CH3 H20 0 00-0113 320 c Inc CH1 CH1 on i on 2 111 011 CH CH:

IV v v:

1130 CH3 HaC CH3 HaC CH3 H20 0 CH3 CH2 H 0 CH3 on, H10 0 0113 OH:

I II/ 1 ll/ l I H/ H 0 0-0113 H20 0 0-011; mo 0 0-cm CH2 0H 0H: on OH: on 25011 011201 on; oo 052 /O OH CH CH5 CH2 CH3 VII VIII H3C\ /CH3 H3C\ /CH3 n20 0 0113 (1H2 mo 7 (fi/CH: CH2 H20 0 o0Hl mo 0 0-0H3 CH2 on o11=0m CH1 0H CH-CHZOH out C-OH CH2 0 CH2 CH3 CH1 CH3 Dihydro-p-ionone (Formula I) which can be made by partial catalytic hydrogenation of [iionone, is caused to react in known manner with alkali amide and acetylene and the acetylene alcohol II reduced to the tertiary alcohol III. The reduction may be effected, for example, catalytically with hydrogen and nickel or with sodium in moist ethereal solution. The tertiary alcohol III yields by reaction with an inorganic acid halide, such as phosphorus pentachloride, accompanied by isomerization, the halide IV which; after reaction with aceto-acetic ester and ketone scission of the condensation product, for instance with barium hydroxide in the usual purification of the product of the saponification, for example by esterification with phthalic acid anhydride and saponification of the phthalic acid ester thus obtained, there is isolated the desired alcohol VIII.

In like manner by starting from dihyd1'o-aionone of the formula an isomeric series of compounds is produced which difier from the products expressed by the Formula I to VIII in the position of the double bond in the ring in the same way that dihydro-p-ionone differs from dlhYdlO-oc-IODOIIB.

The new alcohols find use as such or as intermediate products for making physiologically active preparations, particularly of vitaniine A.

The following example illustrates the invention:

1. 330 grams of dihydro-e-ionone (I) are dissolved in 5 times this weight of absolute ether and there are gradually added to the solution While it is cooled with ice and salt, grams of finely powdered sodium amide. Into this mixture, While stirring, is passed a dry stream of acetylene until the mixture is saturated therewith. To isolate the product ice-Water is added, the ethereal layer is separated and dried with sodium sulfate and distilled. The acetylene carbinol 11 thus obtained boils at 135 C under 10 mm pressure and its specific gravity is d4 :0.936.

2. The acetylene carbinol II is dissolved in twice its weight of ethanol and hydrogenated in presence of a nickel catalyst with hydrogen until 1 mole hydrogen has been absorbed. The quantitatively formed tertiary alcohol III is isolated in the usual manner. It boils at 134 C. under 10 mm pressure and its specific gravity is d4 =0.924.

The acetylene carbinol II may also be hydrogenated by the action of sodiumin moist ether. It is dissolved in 10 timesits weight of ether, an equal Weight of shredded sodium is added and to the whole ice is added, gradually while stirring and cooling, until the whole of the sodium has been dissolved by the water thus introduced. The ter tiary alcohol III obtained in this manner has the same properties as those of the alcohol III obtained by catalytic reduction.

3. The tertiary alcohol III is dissolved in three times its weight of petroleum ether and the solu-- tion is mixed gradually, while stirring and cooling with ice and salt, with one mole of phosphorus penta-chloride. When the reaction is complete thorough washing with water and sodium carbonate solution follow. The chloride IV is sufficiently pure after evaporation of the petroleum ether for being further worked up. It has a chlorine content of 14.8 percent, and its specific gravity is (14 :0976. It decomposes on distilla- 7 tion.

4. 67 grams of sodium are powdered under xylene and then caused to react with a solution of 380 grams of acetoacetic ester in double its weight of benzene until the reaction is complete. The sodium acetoacetic ester thus made is then boiled with 1 mole of the chloride IV until a sample of the mixture no longer gives an alkaline reaction to water. The condensation product which is obtained in a good yield boils at about 165 C. under 0.4 mm pressure. For the ketone scission the condensation product is dissolved in 4 times its weight of ethanol and'the solution is boiled for 2 days with one of 1 times its weight of crystallized barium hydroxide in 10 times its Weight of water. Working up is as usual. The ketone V boils at 130-132 C. under 0.2 mm pressure.

5. The reaction of the ketone V with acetylene is conducted in exactly the same manner as described above under 1. The acetylene alcohol VI thus obtained boils at C. under 0.1 mm pressure and its specific gravity is (14 9:0933.

6. The reduction of the acetylene carbinol VI to the tertiary alcohol VIIis conducted in the same manner as described under 2. The product obtained boils at 124-126 C. under 0.2 mm pressure and its specific gravity is (14 :0914.

7. For obtaining the final product VIII, the tertiary alcohol VII is mixed with 1 times its Weight of acetic anhydride and the mixture is boiled for 20 hours, and the product, after it has been freed from the constituents by heating it in a vacuum to 100 C. is saponified by boiling it with alcoholic lye. From the saponification product the primary alcohol is obtained in the usual manner by heating with phthalic anhydride to 100 C., then filtering and saponifying the phthalic acid ester thus formed; the alcohol is apt to retain halogen, which can be eliminated however by treating the alcohol with sodium in boiling methanol solution. The alcohol VIII forms a viscous oil boiling at l36-138 C. under 0.1 mm pressure. Its specific gravity is (14 :0930.

The series of operations described under 1 to 7 is similar when dihydro-a-ionone is under treatment. The physical constants and the yields of the intermediates and the final product of the a-series expressed by the figures II to VII are nearly the same as those of the B-isomerides II to VII produced from dihydro-{i-ionone. The following values have been found:-

II bio 135C., (120 0.937,

III 2310 134 C., dzo 0.924,

IV chlorine content about 15.0 per cent, dzo

V 120.2 about C. VI 170.1 128 C., dzo 0.934, VII 120.2 124-126 C., (120 0.918, VIII 120.1 136-138 C., dzo 0.929.

What I claim is: 1. Primary diterpene-alcohols of the formula wherein R means a partially hydrogenated benzene ring containing one double bond and one methyl group in oc-DOSitlOll and two methyl groups in od-position to the side chain, which products form viscous oils and are closely related by structure to vitamins A.

2. A primary diterpene-alcohol of the formula H CH CH3 CH3 which product forms a viscous oil of the specific gravity d4 =0.930, boiling at 136-138 C. under 0.1 mm pressure, and is closely related by structure to vitamine A.

which product forms a viscous oil of the specific gravity (14 :0929, boiling at 136-138 C. under 0.1 mm pressure, and is closely related by structure to vitamine A.

LEOPOLD RUZICKA. 

